The Effect of Hepatic Ischemia Reperfusion Injury in a Murine Model of Nonalcoholic Steatohepatitis

• Published in: The Journal of surgical research 2011-07, Vol.169 (1), p.e7-e14
• Main Authors: Tevar, Amit D., M.D, Clarke, Callisia N., M.D, Schuster, Rebecca, B.S, Wang, Jiang, M.D., Ph.D, Edwards, Michael J., M.D, Lentsch, Alex B., Ph.D
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - metabolism; Animals; Diet; Disease Models, Animal; Disease Progression; Fatty Liver - etiology; Fatty Liver - metabolism; Fatty Liver - physiopathology; fatty liver disease; fibrosis; hepatic ischemia; hepatic steatosis; inflammation; Ischemia - metabolism; Ischemia - pathology; Ischemia - physiopathology; ischemia reperfusion injury; Liver - blood supply; Liver - metabolism; Liver - pathology; Male; Methionine - deficiency; Mice; Mice, Inbred C57BL; NAFLD; NASH; necroinflammation; Non-alcoholic Fatty Liver Disease; Peroxidase - metabolism; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - physiopathology; Surgery
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2011.01.056

Background Nonalcoholic fatty liver disease (NAFLD) refers to an increasingly diagnosed condition involving triglyceride accumulation into hepatocytes resulting in a broad spectrum of liver injury. The progression of NAFLD, a relatively benign condition, to nonalcoholic steatohepatitis (NASH) involves the hepatic infiltration of inflammatory cells and subsequent hepatocellular injury. Ischemia/reperfusion (I/R) injury of the liver is a major complication of liver resection, hepatic trauma, and liver transplantation. To date, there have been no studies that have evaluated the effects of hepatic I/R on models of NASH. Objective Evaluate the effects of hepatic I/R on a mouse model of NASH. Methods A mouse model of progressive NASH was developed and evaluated using C57BL/6 mice fed a methionine choline deficient diet for 3, 6, 9, and 12 wk. Mice subsequently underwent 90 min of partial hepatic ischemia with reperfusion of 1, 4, and 8 h. Mice were sacrificed after the indicated periods, and blood and liver samples were taken for analysis. Results Mice fed the MCD diet showed a rapid induction of hepatic steatosis, inflammation, and fibrosis by 3 wk that persisted over the 12-wk period of diet, as demonstrated by histologic examination, alanine aminotransferase (ALT), and liver content of myeloperoxidase (MPO). The response to I/R in livers with progressive NASH fed MCD diet for 3, 6, 9, and 12 wk showed marked neutrophil recruitment and hepatocyte necrosis. Conclusion These data suggest the inflammatory response from I/R is augmented in livers with NASH histopathology compared with normal liver.